Patterns of CAG repeat interruptions inSCA1 andSCA2 genes in relation to repeat instability

Abstract

About 3% of the human genome is composed of simple sequence repeats and many of these sequences occur within genes. These repeats are often polymorphic in a normal population and their expansion in specific genes leads to a number of hereditary neurological diseases. Normal variants of disease‐related genes contain either pure or interrupted repeats, and the postulated function of the interruptions is to prevent repeat expansions. Their structural role in the repeat tracts of genes and transcripts awaits detailed characterization. In this study, we have determined the SCA1 and SCA2 genotypes in a Polish population and found significant differences in allele spectra and frequencies from those reported for other populations. They are discussed in relation to the repeat expansion mechanism and disease incidence. We postulate that the dynamic mutation of the genes SCA1 (also ATX1 or ataxin 1) and SCA2 (also ATX2 or ataxin 2) may begin from the expansion of long pure repeat tracts without the prior loss of interruptions. A simple way of cost‐effective allelotyping of CAG repeat regions in the SCA1 and SCA2genes is also shown. The reliable SSCP/duplex analysis presented here may be the method of choice for the systematic searching of genes for known and novel interrupted repeats. Hum Mutat 24:236–247, 2004.